The introduction of pegaspargase has greatly advanced the treatment of acute lymphoblastic leukemia (ALL). In the literature, only one case of pegaspargase-induced multiple organ failure has been reported, and the patient died due to multiple organ failure.

Herein, we present a rare case of a 40-year-old man with ALL who developed multiple organ failure after treatment with pegaspargase. The patient had two rare phenomena reflecting poor prognosis, including the discrepancy between clinical manifestations and liver function and persistently low alpha-fetoprotein (AFP) levels from subacute liver failure. However, the patient was successfully treated using a multidisciplinary team approach.

This is the first case report of successful treatment of pegaspargase-induced multiple organ failure. The findings emphasize the importance of a multidisciplinary team approach in treating pegaspargase-induced multiple organ failure.

• Pegaspargase
• Multiple organ failure
• Acute lymphoblastic leukemia
• Liver failure
• Case report

Acute-on-chronic liver failure (ACLF) is a liver disease based on chronic liver disease, which is significantly influenced by clinical treatment regimen and disease status, and despite the existence of multiple prognostic assessment indicators for ACLF, the overall sensitivity and accuracy are relatively low.

To investigate the prognostic value of the combined detection of alpha-fetoprotein (AFP), plasma prothrombin activity (PTA), and serum prealbumin (PA) in ACLF.

This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival (n = 47) and death (n = 40) groups according to their clinical outcomes 3 months posttreatment. All the participants underwent AFP, PTA, and PA level measurements upon admission. Baseline data, as well as AFP, PTA, and PA levels, were comparatively analyzed. Pearson correlation coefficients were utilized to analyze the correlations of AFP, PTA, and PA with different survival outcomes in patients with ACLF. Receiver operating characteristic (ROC) curves and areas under the curves were used to evaluate the predictive value of AFP, PTA, and PA for ACLF prognosis.

AFP, PTA, and PA levels were markedly decreased in the death group than in the survival group (P < 0.05). Pearson analysis indicated a positive association of the AFP, PTA, and PA levels with the survival of patients with ACLF (P < 0.05). ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24% and 100.00%, respectively, both of which were notably increased compared to the single-index diagnosis. The ROC of their combined diagnosis was 0.989, significantly surpassing 0.907, 0.849, and 0.853 of AFP, PTA, and PA, respectively. No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection (P > 0.05).

The combined detection of AFP, PTA, and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF, featuring high sensitivity and specificity.

• Alpha-fetoprotein
• Prothrombin activity
• Prealbumin
• Acute-on-chronic liver failure
• Prognostic value

• Acute-on-chronic liver failure
• markers
• models
• prognosis
• progress
• treatments

Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies.

To investigate whether and how AFP could regulate ER stress and hepatocyte injury.

The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence.

High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl₄) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl₄ administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression.

ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

• Alpha-fetoprotein
• Endoplasmic reticulum stress
• Necroptosis
• Apoptosis
• Liver injury

• Animals
• Apoptosis
• Endoplasmic Reticulum Stress
• Hepatocytes/pathology
• Humans
• Liver Diseases/pathology
• Mice
• Necroptosis
• alpha-Fetoproteins/metabolism

To determine the prognostic risk factors of patients with hepatitis B virus related acute‐on‐chronic liver failure (HBV‐ACLF) treated with plasma exchange (PE)‐based artificial liver support system (ALSS), and create a prognostic predictive model.

A total of 304 HBV‐ACLF patients who received PE‐based ALSS were retrospectively analyzed. Potential prognostic factors on admission associated with survival were investigated. Of note, 101 additional patients were analyzed to validate the performance of the prognostic models.

According to 28‐day survival, a total of 207 patients who survived and 97 non‐survivors were identified in the derivation group. Overall, 268 (88.2%) ACLF cases were caused by reactivation of HBV. Cox proportional hazards regression model revealed that age, total bilirubin, ln (alpha‐fetoprotein [AFP]), encephalopathy (HE) score, sodium level, and international normalized ratio (INR) were independent risk factors of short‐term prognosis. We built a model named ALSS‐prognosis model (APM) to predict the 28‐day survival of HBV‐ACLF patients with ALSS; the model APM showed potentially better predictive performance for both the derivation and validation groups than MELD, MELD‐Na, and CLIF‐C ACLF score.

Low AFP was found to be an independent risk factor for high mortality in HBV‐ACLF patients treated with PE‐based ALSS. We generated a new model containing AFP, namely APM, which showed potentially better prediction performance than MELD, MELD‐Na, and CLIF‐C ACLF score for short‐term outcomes, and could aid physicians in making optimal therapeutic decisions.

• AFP
• ALSS
• HBV-ACLF
• plasma exchange

• Acute-On-Chronic Liver Failure
• Biomedical Research/trends
• Humans